Primary, or immunoglobulin light-chain (AL), amyloidosis is a disease of morphologically normal plasma cells. It is characterized by the deposition of amyloid fibrils in various tissues with subsequent death from organ failure occurring shortly after. The fibrils are composed of a monoclonal immunoglobulin (Ig) light chain which has carboxyl-terminal heterogeneity. An associated monoclonal Ig usually occurs in the serum and/or the urine which has lead to the inclusion of AL in the category of monoclonal gammopathies. It is not known at the molecular level whether the plasma cells in AL are truly of monoclonal descent or whether they represent a different category of disease. This project proposes to investigate the molecular basis of AL by genetically defining whether the plasma cells are monoclonal, whether they can be stimulated to either produce Ig or proliferate in response to interleukin-6, and whether the IL-6 receptor can be a target for a cellular toxin. The research design includes the isolation of plasma cells from the bone marrows of 10 patients with AL. Isolation of genomic DNA and Southern blotting with Ig probes will be done on a portion of the cells, as will culturing of the cells with IL-6 and a diphtheria toxin related protein, DAB389-IL-6. The synthesis of DNA, Ig and total protein will be used as outcome parameters. The applicant is an Assistant Professor of Medicine at BUSM in the division of Rheumatology. She qualifies as a D and F applicant as she has not yet had the opportunity to acquire independent research funding. The work described will be performed in the outstanding environment of the Arthritis Center of the Boston University Medical Center (BUSM) where access to a large number of AL patients will be possible. Dr. Raymond Comenzo, a hematologist and stem-cell biologist with expertise in cell isolation techniques, will be involved as a coinvestigator. Dr. John R. Murphy, a noted molecular biologist and chief of the section of Bimolecular Medicine at BUSM will be a collaborator.